Neuromuscular Disease in the ICU

James Allen, MD

I. Guillain-Barré Syndrome

A. Epidemiology: 0.4 - 1.7 per 100,000

B. Cause:

1. widespread inflammatory demylination of peripheral & autonomic nerves

2. central nervous system is spared

3. current hypothesis:

a) infection in a genetically-susceptible host

b) antibodies produced by host which cross react with motor nerve terminal

c) binding of antibody to nerve terminal prevents excitability

d) axonal degeneration from terminal occurs

4. some type of infection preceedes GBS in 50-75% of cases

a) other associations include mycoplasma, pregnancy, HIV, Hodgkin's disease

b) can be associated with Hantavirus infection (Clin Infect Dis. 20:477-8, 1995)

c) can be associated with Hepatitis A (Internal Med. 33:799-801, 1994)

5. Campylobacter jejuni antibodies are found in 35% of patients with GBS compared to 10% of controls (Ann Intern Med 1993)

a) in this regard, the C. jejuni endotoxin core is identical to the terminal tetrasaccharide on GM1 ganglioside (J Exp Med 1993; 178:1171)

b) it is currently believed that C. jejuni accounts for 20-40% of all cases of GBS (Clin Infect Dis 1993; 17:104)

c) patients with C. jejuni infection are more likely to have a protracted course with axonal involvement (N Engl J Med. 333:1374-9, 1995)

C. Presentation:

1. usually symmetric weakness involving peripheral nerves

a) typically ascends from legs to arms and cranial nerves

(1) unusual presentations include arm weakness before leg and bulbar muscles before extremities

b) proximal muscles weaker than distal muscles

c) DTRs absent

2. areflexia

3. mild sensory changes

4. automonic instability

5. EMG shows diminished nerve conduction velocities

a) may be normal early in the disease (in first 2 weeks) and usually lag behind clinical disease

b) fibrillations or motor unit dropout suggests more prolonged recovery

6. CSF protein normal in first few days but steadily rises and remains high for months

D. Course:

1. average nadir = 8 days

2. 29% require ventilation (Clinics in Chest Medicine. 15:705-14, 1994)

3. average duration = 12 weeks

4. 45% develop lower respiratory tract infection & 12% develop UTI (QJM. 88:243-50, 1995)

5. 75% complete recovery

6. 5% relapse

7. 5% mortality (QJM. 88:243-50, 1995)

E. treatment

1. in a double blind study of 242 patients, steroids gave no benefit (Lancet 93; 240:51)

2. HIG as good or better than plasmapheresis (NEJM 1992; 326:1123-9)

a) typical dose = 0.4 grams/kg/day

b) relapse after stopping HIG is common and occurred in 5/7 patients between 1-16 days after treatment in one study; plasma exchange was useful to treat relapse (Neurology 1993; 43:872)

c) in an open study of 25 patients, HIG + methylprednisolone (500 mg/d) resulted in improved 4 week neuromuscular function compared to HIG alone: 76% vs. 53% (Ann Neurol 35:749-52, 1994)

3. plasma exchange was associated with higher 1 year full recovery rate (71%) than control (52%) in 220 patients (Ann Neurol 1992; 32:94-7)

a) there was no difference whether exchange was done with albumin or fresh frozen plasma

b) in this study, 4 exchanges were performed

4. when to intubate?

a) neck flexor weakness correlates with need for mechanical ventilation

b) observation of respiratory pattern helpful but can give a false sense of security

(1) tachypnea

(2) abdominal paradox

c) bedside PFT's should be checked daily

(1) vital capacity usually falls from 40 ml/kg to 15 ml/kg over about 48 hours

(a) normal Vc = 50 ml/kg

(b) < 30 ml/kg associated with inability to cough

(c) < 20 ml/kg associated with atelectasis

(d) patients must be intubated at 15 ml/kg (Am Rev Resp Dis 1991; 144:814-8)

(2) NIF < 20 is associated with rise in pCO2

(a) normal NIF = -70 cmH2O

(b) < 40 cmH2O associated with inability to cough or clear secretions

(3) dyspnea & hypercarbia are late findings

5. other aspects of ICU care

a) careful attention to prevention of pressure nerve compression with frequent turning, pads, etc.

b) autonomic dysfunction common

(1) hypertension - usually responds well to beta blocker

(2) diaphoresis

(3) tachycardia

(4) bradycardia may require pacemaker

II. Myasthenia Gravis (N. Engl. J. Med. 1994; 330:1797-1810)

A. Epidemiology:

1. Prevalence: 1:10,000

2. Female > male 2:1 or 3:2

3. 2 peaks:

a) 20-30 (mostly women)

b) 60-70 (mostly men)

4. Thymomas in 30%; abnormal thymus in 75%

5. Often associated with other autoimmune diseases

6. Mortality is improving, likely due to option for ventilatory support

B. Cause:

1. Formation of IgG to post-synaptic acetylcholine receptor leads to destruction of receptors on the muscle fibres and change of configuration of post-synaptic area (widens with decreased folds)

2. 10-20% of patients do not have detectable antibodies

a) generally felt to be insufficient sensitivity of clinical tests currently available and not an alternative mechanism

3. cause of these antibodies is currently unknown

C. Presentation:

1. Characterized by exacerbations and remissions--two types of exacerbations:

a) Myasthenic crisis: A worsening of myasthenic weakness

(1) Occurs spontaneously or in response to stressors (Infection, stress, pregnancy, fever) or drugs (morphine, quinidine, procainamide, aminoglycosides, Dilantin)

b) Cholinergic crises

(1) uncommon

(2) caused by excessive anticholinesterase medications

(3) may cause respiratory failure

(4) signs: cramps, diarrhea, excessive pulmonary secretions

(5) Tensilon test may worsen weakness

(6) treatment is to withhold medications for a few days

2. Fluctuating weakness--worsens with continued use (fatigues). May be worse with certain muscle groups (i.e. extraocular with ptosis, diplopia)

3. Half present with ocular weakness

4. One third present with dysphagia

5. Rare to present initially with respiratory failure, but it does occur

6. 85% progress to generalized weakness--more proximal, with preserved deep tendon reflexes

7. May worsen or present during pregnancy, especially in the peripartum period--may affect infant

8. Associated diseases:

a) hyperparathyroidism (3-8%)

b) hyperthyroidism or hypothyroidism (either may worsen weakness)

c) other autoimmune diseases (SLE, RA, Graves disease, etc.)

D. Diagnosis:

1. CLASSIC: TENSILON TEST: Brief improvement with administration of edrophonium, 2 mg, repeat with 8 mg if no response

2. REPETITIVE STIMULATION: Decreased action potential with repeated stimulations

3. EMG: Decreased action potential

4. ACETYLCHOLINE RECEPTOR ANTIBODY LEVELS: present in 80-90%--levels do not correlate with disease activity

E. Course:

1. 50% of patients require ICU care at some point in their disease

2. HYPOVENTILATION: Secondary to generalized weakness

a) Often occurs during myasthenic crisis--may be stress-related (i.e. thymectomy, etc.)

b) May occur suddenly or slowly

c) May be difficult to pick up: Can't rely on patient's subjective symptoms

(1) Degree of respiratory failure doesn't necessarily correlate with weakness elsewhere

3. Hypoxemia is worsened by atelectasis

4. Decreases ability to cough leads to increased risk of infection, plugging

5. PHARYNGEAL WEAKNESS:

a) Vocal cord paresis--may have weakened voice, hoarseness, or stridor on exam

b) Increased risk of aspiration, which may further increase with anticholinesterase therapy, which increases secretions

c) Vital capacity is maintained here--can be detected on flow/volume loop (variable extrathoracic obstruction)

6. Respiratory assessment:

a) Vital capacity: Should be > 15 ml/kg

(1) When it falls to < 25% of predicted or less than 1-1.2 litres, consider intubation

b) Peak inspiratory and expiratory forces: When Pe max is < 40, cough is not adequate

(1) If Pe max or Pi max are < 30, the patient generally needs mechanical help

c) Nocturnal desaturation: May have classic symptoms of sleep apnea, orthopnea

d) Hypoxemia: earliest change seen in blood gases--poor prognosis when pO2 < 70

e) Acid/base disturbances: Respiratory alkalosis (early), Respiratory acidosis (late)--consider intubation before this occurs

f) Laryngoscopy: can confirm vocal cord paralysis/paresis

F. Treatment:

1. GENERAL:

a) DRUGS: Anticholinesterases: Mestinon (pyridostigmine) and neostigmine

(1) onset of Mestinon is within 30 minutes with peak effect in 2 hours

(2) maximal dose = 120 mg Q 3 hours

b) Steroids: symptoms may worsen at first--start with small doses (15 - 20 mg/day)

(1) improvement begins in 2 - 4 weeks and is maximum after 6 - 12 months

c) Azathioprine

(1) primarily used as a steroid sparing agent

(2) may take up to a year for effect to be seen

d) Cyclosporin

(1) inhibits T cells

(2) onset of action quicker than azothioprine (usually within 1 - 2 months)

(3) dose usually Å 2.5 mg/kg Q 12 hours

(a) trough blood levels should be monitored

e) PLASMA PHERESIS/EXCHANGE: May help get patients of the ventilator

(1) often done preop for thymectomy

(2) generally see improvement in 48 hours or less

(3) short term treatment with benefits only lasting a few weeks

(4) usually 5 exchanges of 3 - 4 liters over a 2 week period

f) Intravenous immunoglobulin

(1) 400 mg/kg/day for 5 days

(2) same indications as for plasmapheresis

(3) response begins in 4 - 5 days

(4) benefit is temporary, lasting weeks to months

g) THYMECTOMY: Up to 85% improve post procedure (up to ten years later

(1) Post-op course is often difficult (failure to wean secondary to weakness)

(2) Get preop PFT's

(3) Encourage no neuromuscular blockers during surgery, minimal narcs after

(4) Hold anticholinesterases 1-3 days post (some say pre as well)

2. SUPPORTIVE:

a) Use the above measurements plus the clinical picture to guide decision when to intubate/ventilate

b) Some patients with pharyngeal involvement or trouble with secretions may need trach

G. Other lung diseases associated with myasthenia gravis

1. INTERSTITIAL LUNG DISEASE: possibly related to immune complex deposition

2. BRONCHOCONSTRICTION secondary to anticholinesterase therapy--controversial whether this occurs in patients without underlying reactive airways

a) Atrovent may help with this and with increased secretions

 

last updated 3/26/96

 

 

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